The “Uberification” of mRNA: A Conversation With Joseph Payne
Joseph E. Payne, is the President and Chief Executive Officer of Arcturus Therapeutics. He brings with him an exceptional track record of ushering novel therapeutics to the clinic including targeted RNA medicines utilizing lipid-mediated delivery technologies. Payne’s background includes over 20 years of successful drug discovery experience at Merck Research Labs, DuPont Pharmaceuticals, Bristol-Myers Squibb, Kalypsys, and Nitto as evidenced by over 40 publications and patents, and several investigational new drug (IND) clinical candidates. His academic training includes a Bachelor's Degree in Chemistry from Brigham Young University, a Master of Science in Synthetic Organic Chemistry from the University of Calgary and Executive Training Certification from MIT Sloan School of Management.
Asher Joy (BT): Business Today focuses on connecting undergraduates with the “business world”, of which there are very many different definitions. So, could you start off by giving your background, and explain your journey starting out as an undergraduate chemistry major to now being the founder and CEO of Arcturus Therapeutics?
Joseph Payne (JP): I began my career as a scientist. I was always interested in medicine as well, but, as I was preparing for either grad school or medical school, I found that the lab was more enjoyable than I had anticipated and the hospital setting was less enjoyable than I anticipated. So I ended up focusing on science. I was always very excited about the innovative opportunities and the creative elements and how you can make a significant impact in people's lives and life in general. I ended up in the world of lipid nanoparticles which evolved into messenger RNA (mRNA) delivery systems and these relatively sophisticated therapeutics platforms. After I got a graduate degree in synthetic organic chemistry, I began my career in the industry on the East coast working in large pharma and got a lot of great exposure. I worked with companies like Dupont Pharm, Bristol-Myers Squibb and then I transitioned to a Japanese company called Nitto Denko Technical Corporation. That’s where I really started to focus on RNA and lipid nanoparticles. At the time we did not have the kind of scientific understanding we have now. There was nothing even close to being a drug that involved these nanoparticle delivery systems.
Back in 2012, not many organizations saw the value of RNA as a viable therapeutic option; hundreds of millions of dollars were spent by many companies exploring the technology. While some developments were made, not many companies were successful and had to discontinue their research programs. At that time, while I was at Nitto, we were learning that these liquid nanoparticle RNA therapeutics may have real potential- We were going against the tide, but I was convinced of the sea change that RNA therapeutics could bring. It was such a niche field. During this time Pad Chivukula, Arcturus’ Chief Scientific Officer, and I were feeling entrepreneurial and in 2013 we decided to quit our jobs and start Arcturus Therapeutics. Fast forward another eight years and Arcturus is a thriving, publicly- traded company here in San Diego.
BT: Was your interest in founding Arcturus motivated by wanting to be the company that was doing what other companies weren't or did you have another source of inspiration?
JP: 20 years prior to setting up Arcturus, I had always wanted to start a company. I recognized that there's many different elements that need to fall in place before doing so. I saw that you need to have the right people, the right idea, the right time and, of course, you need the money--right, resources. Finally in 2013, my other co-founder and I had the people, resources, and the idea of creating a safe and effective delivery vehicle for messenger RNA. We believed that RNA molecules are the future of pharmaceuticals, and we genuinely felt and believed that and had passionate desires to make an impact with respect to RNA medicine therapeutics.
BT: As a CEO, do you still find that you’re able to do more lab-type work or have you evolved into a more managerial role?
JP: When I started the company, I was in the lab 24/7, and I really loved that experience. Now, I focus more on the idea generation, whiteboarding these ideas around the nanoparticle design. I focus on how we make everything, lipids or RNA, better. I do miss the lab as I don’t see it as much. But I do visit it and I put on the white coat and there's media -- you've seen these articles -- where the CEO is walking around the lab with glasses on. Unfortunately, my commitments to developing the company and taking us on a path towards success has taken away my ability to be in the lab, but I regularly interact with our scientists who get to have all the fun in the lab. In the lab there's value being created by these brilliant scientists. I'm jealous, I want to be in there in the lab, but our scientific development is in the very capable hands of our scientists!
BT: Transitioning more toward what Arcturus does, can you explain what its core technology platform really is, this technology which delivers therapeutic RNA or DNA to target cells inside a patient's body?
“...an mRNA molecule is a very long, highly charged molecule. It’s like a shoelace that has a bunch of negative charges — it’s a beautiful complex, large, long stringy molecule.”
JP: Our core technology is the LUNAR® delivery technology. Thankfully, everyone now knows what messenger RNA is because half of us have been injected with it. So, there is a lot more familiarity with the term and that it has at least a reasonable application in vaccines. Certain details might be missed. As an example, an mRNA molecule is a very long, highly charged molecule. It's like a shoelace that has a bunch of negative charges -- it’s a beautiful complex, large, long stringy molecule. It codes for proteins that are essential for sustaining life; a molecule that contains the code of life, but is also somewhat unstable in its natural form. If I touch messenger RNA, it degrades; if I put it in saliva, that will destroy it in seconds; blood destroys it in seconds.
Considering this, it doesn't sound like a good therapeutic if blood, saliva, heat, and oxygen rapidly degrade it. This is why you have to find a way to safely and effectively deliver this molecule to where it needs to be in the body. If you can safely and effectively get messenger RNA to where it needs to be it could be disruptively innovative for the pharmaceutical industry, meaning that we will have entirely different ways to think about treating disease, because messenger RNA by itself is beautifully perfect, it can make whatever you need biologically -- like an antigen for a vaccine response (as the case for COVID-19 mRNA vaccines). Everything in our bodies is made by messenger RNA, so if you're missing something you can make it, and we can fill in if there’s a missing protein or dysfunctional enzyme, for example. We can deliver an mRNA and replace it.
But like I said, mRNA is very difficult to get to where it needs to be safely and effectively and that's why LUNAR® technology is transformative. This technology is designed with multiple ingredients in the shape of a very small sphere. That's why we call it a nanoparticle; it is very tiny. And inside this tiny nanoparticle is the messenger RNA. We design the particle to transport this very important payload to where it needs to be. They’re 200 different cells in the body, and Arcturus is good at getting messenger RNA into three or four types. We can get it into muscle cells through an injection like what we do with the vaccines. The particles are taken up by myocytes and it is transported into the cell and this is where they release the payload and then the magic happens, and the mRNA makes antigens or other proteins of interest.
We're also good at delivering to hepatocytes, cells in the liver. They're accessible intravenously. Then for the third cell type, we have an inhalable technology, for which we've designed these particles to survive an aerosolization process, so you can breathe them in and then gain access to what are called bronchial epithelial cells. Once you get in there, you can make the protein of interest, for example, to help patients suffering from cystic fibrosis. The goal of Arcturus is to safely and effectively deliver messenger RNA to where it needs to be, and that is the value of our LUNAR® delivery technology.
BT: Focusing on Arcturus’s involvement with developing mRNA vaccines, what exactly differentiates your vaccines from others that use mRNA, for example, by providing a lower dosage or not requiring very cold temperatures for storage?
JP: What makes our vaccine candidates different from the others is that we are using the next generation mRNA technology. Conventional messenger RNA is what is being used in vaccines which is the modality being distributed right now. We're using the next generation technology called self-amplifying mRNA. This next generation technology is exciting because it can lower the dose requirement, which is a key differentiator. Lowering the dose level has several prospective benefits -- from a manufacturing perspective you can be much more efficient and make doses for large population diseases like COVID-19, as well as from a safety perspective in that the toxicity may be less compared to the vaccines that are given in larger amounts/dose. Also, our final product is not a frozen liquid, but rather a lyophilized product, which means the water has been removed so our product looks like a dry powder. To that you then add water prior to injecting the vaccine. Because the supply chain involves a powdered material, rather than a frozen liquid, we may not require minus 70°C storage, which is advantageous.
The key advantage, I believe and as I said, is the dose level. As data will continuously be collected, I think there's advantages to having ideally the same efficacy or the same profile, but a lower amount being injected. And with the self-amplifying mRNA, we've seen pre-clinically in animals very clear and strong evidence that self-amplifying messenger RNA produces a stronger cellular immunity profile. This is important because that means, theoretically, we could potentially have a longer lasting vaccine. So, as people go into the next few years and get their booster shots, people are going to care more and more about a safer, long-lasting vaccine.
BT: Previously, in 2020, you mentioned that we're in this “horse race” to get to the finish line of vaccine approval and deployment. Now that many vaccines have been approved, how close do you think we are to getting to the finish line from a global perspective?
“So, in this regard there are many races, if you will, against these infectious diseases. We’re always going to have to rapidly update the vaccine platform technology for the present variant of concern.”
JP: I think we all may have been eager to remedy the pandemic with a viable vaccine. What we've now come to realize is that there's no finish line and unfortunately, we've now learned that COVID is likely here to stay. We are in it to try to help populations be protected against COVID like other vaccine companies. We imagine it's going to become more like the flu and less like polio. It's more like the flu, meaning that it's global, and it's always changing. So, in this regard there are many races, if you will, against these infectious diseases. We're always going to have to rapidly update the vaccine platform technology for the present variant of concern. For example, our most advanced vaccine was designed with variants of concern like Delta in mind. That's being developed right now in Phase III trials in Vietnam and we're guiding that. We aim to file an emergency use authorization in Vietnam in December so that's just around the corner. We’re hoping that we can help the citizens of Vietnam, which has over 100 million people -- so this is a very substantial market, and meaningful for a company of our size.
BT: Would you say that what you’re doing in Vietnam is similar to what you've also done, in Israel and Singapore, but at a different scale?
JP: We’re presently conducting Phase I/II booster trials in Singapore with our latest version of our vaccine and in Vietnam we’re conducting a Phase III vaccine efficacy trial. With Israel, we have a supply agreement relationship, and if any of these trials prove to be fruitful and successful, then this vaccine might be an excellent booster and because we have a relationship with Israel we would offer to help them with boosting. Some people are considering getting a third shot of an approved vaccine, and we hope one of the choices will be a shot of Arcturus.
BT: To end on a light-hearted note: when you wake up to go to work, what is the number one thing that excites you?
JP: I'm a scientist at heart. There’s a side of me where I am genuinely passionate about innovation, and I genuinely believe that messenger RNA is not only going to disrupt the vaccine space, as we're seeing happen right now. But we're going to move on to the flu shot and disrupt that, as a community of messenger RNA companies. I look forward to building life by building these molecules and restoring protein in people to have a meaningful clinical impact-- ultimately helping patients. I think there’s an amazing opportunity here over the next couple decades where we're going to see messenger RNA be like Uber- and change how things are done. We’re going to “uberify” the way things are done, and it's good to wake up every day, knowing that you're not just part of helping a lot of people but also that there's a competitive excitement in disrupting a field through bringing vaccines and therapies that aren’t currently available to those patients who need them.